Published in Metastatic Breast Cancer · April 08, 2022 .... CDK4/6 Inhibitor Outcomes in Patients With Advanced Breast Cancer With Germline Pathogenic Variants in DNA Repair–Related Genes
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"This retrospective study assessed the prognostic value of germline pathogenic variants in DNA repair–related genes among patients with advanced breast cancer treated with CDK4/6 inhibitors plus endocrine therapy. The authors found that among patients with germline DNA repair gene mutations (specifically gBRCA1/2-ATM-CHEK2 mutated), treatment with CDK4/6 inhibitors was associated with poorer outcomes versus those tested without these mutations (gBRCA1/2-ATM-CHEK2 wild type).
This study demonstrated that CDK4/6 inhibitors may be less effective in patients harboring germline BRCA1/2-ATM-CHEK2 pathogenic variants."
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Hazelgreen
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As far as I know, I am neither. However, I've never had genetic testing as such. Have you had genetic testing?
My oncologist did tell me, after he received the results of my liver biopsy that it indicated that I had a mutation which supported the use of Piqray. He was pleased to know that because it means he can give me another pill once ribociclib fails. However, I understand that the side effects of Piqray are worse than the side effects of Kisqali so I'm not looking forward to that possibility.
A year in, or two, oncologist ordered a full range of genetic testing of my original tumor. -- I am half Ashkenazi, so should have had BRCA test when first got bc. (I have an extremely Irish name, so I think the docs forget that is not the whole story.) Not that. (The one person I know who turned out to have BRCA is anti-semitic, so apparently genetic group is not dispositive. She has had a really rough ride with her breast cancers, but it is not metastatic.) I was disappointed I have no mutations whatsoever. That means they can't do any more specific targeting of meds. If your oncologist said you have the mutation that supports Piqray, then they must have done genetic testing of a tumor. No other way to know it. It is a good thing, more options; more life.
A small percentage of breast cancers are inherited -- all cancers are genetic mutations, but only 10% or less are inherited mutations. BRCA is autosomal dominant, meaning if either parent has the mutation, you will, but you will not necessarily get cancer.
Why am I telling you this? All you said was that you didn't know it was associated with Jewish heritage. It isn't -- it is only Ashkenazi, i.e., Eastern European. Personally, one of my grandmothers was born in Latvia, Jewish, and my grandfather, her husband, was born in Bridgeport, by way of England, but his family was from Poland. I did not get the BRCA genes from them.
My other grandfather was of Irish descent and my other grandmother's ancestors were from Northern England. There I did luck out genetically. The auto-immune disease I had before cancer was misdiagnosed and misdiagnosed and I had such excruciating weird pain, an ice pick head ache, couldn't open my mouth, disturbed vision, and falling asleep if I sat down. I finally googled it myself and found a column in a British newspaper. Turns out to be genetic and more common among Nordic people and those from Northern England, especially women. Because of the failure to diagnose it early, it is often discovered when someone shows up in an ER suddenly blind in one eye, over 50. I caught it before that happened. (I never met that branch of the family and cannot find them. The name is quite common and they were estranged from us.) For a few years, I proselytized, telling every woman I met who might meet the criteria, every man who had a wife who had that genetic history, to beware, because most doctors do not think of it.
It seems you and I share Irish heritage. My maternal grandfather came from Ballymoney, Northern Ireland in 1871 (my middle name is Dempsay). He married Ida Lucinda Virgin whose ancesters migrated to Canada from the eastern seaboard of the USA. The Virgins can trace their ancesters back to England in the 1600s. Ida's mother may have died from cancer in 1909 as my mother remembered her from the peppermints she constantly ate as a pain reliever. If she did, she may have passed on some sort of suceptibility as one of my maternal aunts died from breast cancer in 1957. I am lucky to have a bound family history to consult as my younger sister did a great deal of work to write a detailed history of my mother's family, starting with SJ Dempsay who had 17 children.
I don't know much about my own individual genes but, thinking again, given the huge size of the Dempsay family, my MBC may just reflect the fact that 4.5% of women end up with MBC so someone in my family was bound to have it, and that someone happens to be me.
hi Cindy. thank you for this. interesting. 'testing' makes so much sense to me. and perhaps testing already takes place much more than i am aware. just starting to learn more.
Thank you for sharing this, although it is disappointing to read this. I actually have the CHEK2 gene as do my sisters and one of my brothers. It was found after I found out about my MBC. I have been doing well on Ibrance and Letrozole and hope to continue doing well despite this gene mutation.
It's good to remember that statistics are just probabilities calculated over reasonably large numbers of people. Clearly, some people with the CHEK2 mutation did well on Ibrance and letrozole, and you are most likely in that group.
That is definitely my hope! My youngest sister who also has this CHEK2 gene was recently diagnosed with Breast Cancer. She opted for a double mastectomy and is on letrozole. My other sister also has the gene but does not have breast cancer but is going to have a double mastectomy as a preventative measure as her doctor said it is not a matter of if she will get breast cancer but when she will get it. I guess this is a newer gene they have discovered that can cause breast cancer.
Unfortunately, for your sisters, there are no guarantees with mastectomies. My reading of the European research literature in 2006 persuaded me not to have the mastectomy recommended by my oncologist. In 2019, I had many mets throughout my spine, lungs, spleen, lymph system, but nothing has ever shown up again in a breast. Breasts (ducts or lobes) may be the source of breast cancer but it seems the main problem occurs after the cancer components (cells or?) leave the breast via the lymph or blood systems. The movement out of the breast may, as it clearly did in my case, happen before the breast tumour is large enough to be seen on a mammogram.
Hi Cindy--If your biopsy/genetic tests show that you have the PIK3CA gene wouldn't they have also tested for the BRCA genes? My tumor samples were sent to Strata Oncology and they ran a huge panel. How would they just test for the PIK3CA on your liver biopsy sample and not the other genes? Hmmmmm?????? Kay
I don't have a clue, Kay. When I speak to my oncologist again (it may be three months from now), I'll ask him if he received a complete genetic workup from the biopsy of the liver tumour last spring. I thought I had a copy of everything on my file at the Cancer Centre, but maybe I don't. The oncologist just made the remark about the PIK3CA gene in a passing comment in a telephone contact a couple of months ago, and I thought that was all he was told. I will try to learn more about genetic profiling in general since as Carole mentioned above, perhaps more such testing is taking place than we are aware of....
Do you know where your tumor was sent? The big companies are Guardant, Foundation One. According to my copy of results--and from what I know about the science--they scan for hundreds of genetic markers. On my report they tested for "targeted genomic alterations" in 121 genes--and on the first page it sounds like there was not enough specimen to adequately examine everything. My oncologist at that time said they could not test for which estrogen blockers were most effective, however, ladies on FaceBook say they have gotten that information from the Guardant or Fndn One testing. Mine is a multiple page report. I hear that they do not even have any treatments for some of the genes tested for. I think these studies cost thousands--I was at a lecture before the pandemic where the oncologist listed the companies and the costs--mine was at no charge to me because the hospital has some kind of program/agreement with this company. That is all I know!! Best! Kay
hi Kay. that is disturbing to me that they have the capability/technology to determine which estrogen blocker is 'most effective' and yet they are not routinely using that very important intel. at least not where i go. and always about the money. we truly are guinea pigs. makes me angry. and sad. this is our lives at stake. i bet if it was their mother, sister, wife they would be testing regardless of the cost. my thoughts.best wishes....
Hi Carole--Yes, i agree. I am not 100% sure of any of the above--however, there is one woman on FB whose posts I have seen a number of times--who tested that she did not respond to the AI's and only to fulvestrant. She keeps stressing to everyone to get tested!! The cost of the genetic studies is somewhere around $5000--but a PET costs about the same. So must be easier to just "try things"--try a drug and see if it works--which is what I see happening to anyone who has become resistant to the AI's or e-blockers, just try the next drug. It seems to be the route. No testing available at the later stages of our disease--so maybe they just plow thru the early treatments the same way. Advocate, advocate--and see where we can have a say and get things changed. What we really need is better drugs with fewer side effects. Best to you! Kay
Kay. i hear you. and what about research for mbc....5% only when we make up 30% of the population of breast cancer. can you imagine what they could do with 25% more of that billions of dollars of donated money to breast cancer. maybe a cure???
Yup--keep getting the word out and have people donate to Metavivor--where 100% of the donations go to research. Every year I post that info on my FB page, ask for donations, send $ to Metavivor myself. I was in a Metavivor support group--and they would hold masked balls to raise $--before the pandemic. So much more to be done. We are so sick, and yet have to raise awareness for ourselves. But try and get over the anger part--I have been taking a class on renewing life--we all also need good mental health! K
my sister makes a yearly donation in my honor since 2013 and would ask me where i wanted it to go. i found metavivor several years back and now she knows where to send. I'm lucky to have her💛
Hi Kay,Given your well-advised comments, I reviewed all my oncologist's reports. This is what I learned. Last May 19th, the section of his report titled, "Diagnosis" stated that a liquid biopsy had been done and "No actionable mutations detected". He then stated that the "CT-guided liver biopsy" confirmed that the cancer in the liver is ER+HER2-. The next six monthly reports all repeated the exact same comments (computer files have really reduced the time involved in generating patient reports).
Then, the Jan 12th report added one simple line to the "Diagnosis" section: "PIK3CA mutation: Positive". I think, during that telephone call he told me that he was able to get a free analysis of my liver sample, and was pleased that there was another treatment for me once ribociclib failed before I would have to move on to chemotherapy. I didn't question him as to the source of this "free tissue analysis".
When I googled the PIK3CA mutation, I came across an ad from Novartis which indicated that physicians could obtain a free bioanalysis of tissue samples to determine whether their patients had the PIK3CA mutation (up to 40% of breast cancers have this mutation). Novartis manufactures Piqray, the targeted drug for the PIK3CA mutation so it certainly is in that company's best interests to have more patients take Piqray. In my case, I think Novartis provided the anaysis and the sample was only tested for the PIK3CA mutation.
I think, Kay, that neither my original spleen biopsy nor my liver biopsy received the detailed examination yours received. I think all that was done was to confirm the type of breast cancer. The type of report you mentioned is far too expensive for a socialized health system to provide. Although I'm still trying to learn more about the subject, I'm not yet convinced, in any case, that genetic testing can tell us which targeted drugs will work best for each of us. Then, as you well know, there are still all those side effects with no guarantee of effectiveness.
Hi Cindy--I agree with your assessment 100%. Good research!! From reading about the experiences the ladies on FaceBook have shared, their insurance companies often do not cover the genetic analysis of the tumor specimens. Some have not asked for or approved of the samples being sent, and have gotten billed--and had struggles getting someone else to pay. So the insurance companies here in the US are not paying for these studies either. I should ask my new oncologist if the genetic studies can predict which targeted E-blockers are effective. You'd think there would be some way to write and ask the genetic analyses companies themselves. There is one woman on FB that just insists that this is important--and I think she is a former nurse. The lecture I heard in Nov. of 2019 (given by one of the U of MN research oncologists--she was one that I could have seen) did not say anything about detecting that information. BTW--the lecturing oncologist did say that treatment with the AI's causes resistance. And that with E-pos MBC, the mets have more mutations than the primary tumor. Good your onc did the liquid biopsy. She said some mutations are in the tissue and not in the blood--and if the tumor is being treated, different parts may test out differently--so better to take the sample when the tumor is not being treated. (Do I sound like a former lab researcher here? Ha!) She said they can check for lots of gene mutations that they either do not have drugs for, or the drugs are not yet approved. I got that the usefulness of these tests was very much still in the research stages. That was Nov. 2019.....there might be new info by now! Have a great day!
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